Percutaneous transluminal coronary angioplasty has been widely performed as a therapeutic method for ischemic heart diseases. However, it is known that restenosis occurs in 30 to 50% of patients after three to six months after the operation due to intimal thickening. A method was developed in which a stenosis lesion is expanded with a balloon catheter, and then a stent is indwelled, and thereby the frequency of restenosis was decreased. However, restenosis is still observed in 10 to 30% of such patients, which arises a problem (N. Engl. J. Med., Vol. 331, p. 489 (1994)).
Thrombogenesis and abnormal proliferation of vascular smooth muscle cells due to intimal damage are considered as major causes of intravascular pachymenia and restenosis caused thereby (Nature, Vol. 362, p. 801 (1993)). In recent years, drug-eluting stents coated with sirolimus or paclitaxel, which has an antiproliferative action against vascular smooth muscle cells, have been developed. Although it has been reported that both drug-eluting stents exhibited significant inhibitory effects on restenosis compared with conventional stents, restenosis is still observed in a little less than approximately 10% of patients (N. Engl. J. Med., Vol. 349, p. 1315 (2003); N. Engl. J. Med., Vol. 350, p. 221 (2004)).
The mitotic kinesins are proteins that are involved in the mitotic spindle regulation, and play an essential role for progression of the mitotic phase in cell cycle. The mitotic kinesin Eg5, one of the mitotic kinesins, is a bipolar homotetramer molecule, and is known to be involved in the formation of the bipolar spindle structure by crosslinking two of microtubules of the same direction and moving them in the direction toward the + (plus) end to cause sliding of two of the antiparallel microtubules, thereby keep − (minus) ends of microtubules at a distance and separate spindle pole bodies [Cell, Vol. 83, p. 1159 (1995); J. Cell Biol., Vol. 150, p. 975 (2000); Jikken Igaku (Experimental Medicine), Vol. 17, p. 439 (1999)]. Therefore, Eg5 inhibitors are considered promising as therapeutic agents of diseases relating to cell proliferation [WO2001/98278; WO2002/56880; WO2002/57244; Trends in Cell Biology, Vol. 12, p. 585 (2002)]. As Eg5 inhibitors, there are known, for example, quinazolin-4-one derivatives (WO2001/30768, WO2003/039460, and the like), triphenylmethane derivatives (WO2002/56880), thiadiazoline derivatives (refer to Patent documents 1 to 4), and the like.
There are further known thiadiazoline derivatives having an antitumor effect (see, Patent document 5).    [Patent document 1] International Patent Publication WO2004/092147    [Patent document 2] International Patent Publication WO2004/111023    [Patent document 3] International Patent Publication WO2004/111024    [Patent document 4] International Patent Publication WO2005/035512    [Patent document 5] International Patent Publication WO2003/051854